Piperidine → Benzyl 2-(hydroxymethyl)morpholine-4-carboxylate

HRID 2300805Notes

Reaction equation

HRID 2300805 reaction equation
[C:1]1([O:14][C:15]([N:17]2[CH2:22][CH2:21][O:20][CH:19]([CH2:23][OH:24])[CH2:18]2)=[O:16])[C:13]2[CH2:12][C:11]3C(=C[CH:8]=[CH:9][CH:10]=3)C=2C=CC=1.N1CCCCC1.C(N(C(C)C)CC)(C)C.ClC(OCC1C=CC=CC=1)=O>C(Cl)Cl.CCOC(C)=O>[CH2:1]([O:14][C:15]([N:17]1[CH2:22][CH2:21][O:20][CH:19]([CH2:23][OH:24])[CH2:18]1)=[O:16])[C:13]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1

Participants

7

Reactant 4

HCID 8082PiperidineHCID 10387Benzyl chloroformateHCID 81531DiisopropylethylamineHCID 18354390HCID 18354390, compound

Product 1

HCID 3496524Benzyl 2-(hydroxymethyl)morpholine-4-carboxylateYield 37.5%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2.20 g of 4-fluorenyloxycarbonyl-2-hydroxymethyl morpholine in 25 mL of CH2Cl2 was added 1.29 g of piperidine. The mixture was stirred at room temperature for 2 days. Diisopropylethylamine (7.15 g) and 6.30 g of benzyl chloroformate were added and the mixture was stirred overnight at room temperature, then diluted with 100 mL of EtOAc and washed with 50 mL each of 1 N HCl, saturated NaHCO3, and brine, dried over MgSO4, and concentrated. The residue was purified by flash chromatography, eluting with a gradient system of 20:1 CH2Cl2-acetone to 9:1 CH2Cl2-acetone, to yield 638 mg of the title compound.

Workup

  1. stirringthe mixture was stirred overnight at room temperature
  2. washwashed with 50 mL each of 1 N HCl, saturated NaHCO3, and brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. customThe residue was purified by flash chromatography
  6. washeluting with a gradient system of 20:1 CH2Cl2-acetone to 9:1 CH2Cl2-acetone

Sources & evidence

ORD record
ord-6f16fbab7e1648d082a4bad25ac81434
Source dataset
uspto-grants-2002_12
Patent number
US06498165B1

Reaction notes

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